Nab-paclitaxel plus cisplatin versus docetaxel plus cisplatin and 5-FU induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: A multicenter parallel controlled phase III trial.
Authors: Xing Lv, Qi Zeng, Weijun Zhang, Hao Cheng, Weixiong Xia, Xiang Yanqun, Hu Liang, Xun Cao, Xi Chen, Zejiang Zhan, Ying Deng, Jiayu Zhou, Lulu Zhang, Chixiong Liang, Haoyang Huang, Yingying Huang, Zhuocheng Cai, Xiang Guo
Journal: Journal of Clinical Oncology (2023)

6071 Background: Although several large phase III clinical trials and meta-analysis have demonstrated significant clinical benefit of docetaxel combined with cisplatin and 5-FU (TPF) chemotherapy in head and neck cancer, serious adverse reactions are unsatisfactory. Therefore, this study was designed to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin (TP) versus TPF induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: In this open-label, phase 3 trial, patients were randomized 1:1 to received TP (260 mg/m 2 nab-paclitaxel and 80 mg/m 2 cisplatin on days 1 and 22) or TPF (60 mg/m 2 docetaxel and 60 mg/m 2 cisplatin on days 1 and 22; 3 g/m 2 5-Fu on days 1-5 and 22-26) every 3 weeks for 2 cycles, both groups of patients received CCRT (100mg/m 2 cisplatin and IMRT on days 43 and 64) every 21 days for 2 cycles. The primary endpoint was failure-free survival. Secondary endpoints included overall survival, objective response rate (ORR), quality of life and safety. Results: From January 2019 to July 2021, 281 patients were randomized to TP (n = 142, TP arm) or TPF (n = 139, TPF arm). The median age was 44 years (range, 20-63) in the TP arm and 45 years (range, 18-69) in the TPF arm. The pathological stages were 40.85% stage III and 59.15% stage IVA in the TP arm, while those of the TPF arm were 43.17% stage III and 56.83% stage IVA. There were 99.30% and 97.12% undifferentiated nonkeratinizing carcinoma in the two groups, respectively. All patients had Karnofsky performance status of 90. ICT was completed in 98.93% (100% in the TP arm and 97.84% in the TPF arm). The median relative dose intensity of nab-paclitaxel and cisplatin were 99.96% and 99.81% in the TP arm, 99.83%, 100% and 100% for docetaxel, cisplatin and 5-FU in the TPF arm, respectively. The ORR were 80.28% in the TP arm and 78.26% in the TPF arm after two cycles of ICT. 85.77% (83.10% in the TP arm and 88.49% in the TPF arm) completed the CCRT. After two cycles of CCRT, the ORR were 99.25% and 99.24%, respectively. 3 months after completion of all treatment, the ORR were 99.25% and 99.25%, respectively. During ICT, all treatment-related adverse events occurred in 40.14% of patients in the TP arm and 57.55% in the TPF arm. The most frequent grade 3 adverse events were neutropenia (0.70% vs 2.16%), leucopenia (0 vs 2.88%), diarrhea (0 vs 0.72%) in the TP arm and in the TPF arm. Over the entire course of treatment, the most common was 1 grade adverse events, and no patient developed grade 4 adverse events in the two groups. Conclusions: In this study, TP regimen showed similar trends in the ORR but excellent safety profile in patients with LA-NPC compared with TPF regimen, suggesting a potential therapeutic option for this population. Clinical trial information: ChiCTR1800019922 .